Regorafenib (Stivarga) — Clinical FAQs

Question 1

What is Regorafenib FDA-approved to treat?

Accepted Answer

Regorafenib is FDA-approved for the following oncology indications: 1. Metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, anti-VEGF therapy, and anti-EGFR therapy (if RAS wild-type) — approved September 2012 (CORRECT trial) 2. Locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) previously treated with imatinib and sunitinib — approved February 2013 3. Hepatocellular carcinoma (HCC) previously treated with sorafenib — approved April 2017 (RESORCE trial).

Question 2

How does Regorafenib work (mechanism of action)?

Accepted Answer

Regorafenib is an oral multi-kinase inhibitor that targets a broad spectrum of kinases involved in tumor angiogenesis, oncogenesis, and the tumor microenvironment. Its primary targets include VEGFR1, VEGFR2, and VEGFR3 (anti-angiogenic), TIE2, PDGFR-β, and FGFR1 (vascular remodeling), KIT, RET, and RAF1/BRAF (oncogenic signaling), and MEK (downstream MAPK pathway). Regorafenib is structurally similar to sorafenib, with a fluorine substituent that broadens its kinase selectivity profile. The combined inhibition of VEGFR-mediated tumor vasculature formation and RAS-RAF-MEK oncogenic signaling cascade results in impaired tumor growth, invasion, and metastasis across multiple tumor types.

Question 3

How is Regorafenib administered?

Accepted Answer

Regorafenib is administered Oral (PO). Regorafenib 160 mg PO once daily for the first 21 days of each 28-day cycle (3 weeks on, 1 week off).

Question 4

What are the most common side effects of Regorafenib?

Accepted Answer

The most commonly reported side effects of Regorafenib (≥10% incidence) include: Hand-foot skin reaction (HFSR)/palmar-plantar erythrodysesthesia (47-67%), Fatigue/asthenia (64-69%), Hypertension (30-59%), Diarrhea (34-43%), Decreased appetite (47-49%) and others (13 total). Consult your oncologist for complete prescribing information.

Question 5

Does Regorafenib have a black box warning?

Accepted Answer

Yes. Regorafenib carries FDA black box warning(s) regarding: 1. Hepatotoxicity: Severe and sometimes fatal hepatotoxicity has occurred. Monitor LFTs prior to initiation, every 2 weeks during first 2 months, then monthly. Withhold for ALT/AST >5× ULN; discontinue if ALT/AST >20× ULN or if hepatotoxicity with bilirubin elevation >2× ULN persists.

Question 6

Is Regorafenib safe during pregnancy?

Accepted Answer

Regorafenib pregnancy safety: Pregnancy Category D. Regorafenib causes embryo-fetal toxicity and teratogenicity. Women of reproductive potential should use effective contraception during therapy and for 2 months after last dose. Male patients with female partners of reproductive potential should use contraception during therapy and for 2 months after last dose. Breastfeeding is not recommended.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

Regorafenib — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms